Murine L1210 leukemia cells resistant to L-phenylalanine mustard (L-PAM) can be sensitized in vitro and in vivo to L-PAM by reducing the cellular concentration of the tripeptide glutathione. Such reduction can be accomplished in vivo by implementation of either nutritional or pharmacological regimens. Nutritional reduction of tumor cell glutathione is accomplished by short term (1 week) maintenance of host animals on defined amino acid diets devoid of L-cystine and with L-methionine reduced to 25% of control. These results indicate a preferential reduction of tumor cell glutathione and selective sensitization of the resistant tumor cell to L-PAM when compared to host bone marrow progenitor cells. Pharmacological reduction of tumor cell glutathione can be achieved by constant infusion, from alzet mini-osmotic pumps, of D,L-buthionine-S, R-sulfoximine, an inhibitor of glutathione biosynthesis, into tumor-bearing mice.